The National Lung Screening Trial (NLST), launched in September 2002, continues to be a critically important component of the NCI goal to eliminate death and suffering from lung cancer. Unfortunately, lung cancer remains the leading cause of cancer death. To date, randomized controlled trials of screening modalities such as chest x-ray and sputum cytology have not demonstrated any impact on lung cancer mortality. Therefore, without effective screening or substantive improvements in effective therapies little progress has been made in lowering lung cancer mortality. Promisingly, technological advances, specifically, the advent of low-dose techniques with rapid, computerized helical computed tomography, have allowed detection of smaller lung nodules. Other potential early detection strategies such as serum, plasma and sputum biomarkers are currently preliminary, and require substantial refinement and validation before examination in a randomized, controlled trial for lung cancer screening. The NLST will determine whether the most promising current strategy for early detection, low-dose helical CT (LDCT) lowers lung cancer mortality. The NLST was designed to detect a 20% or greater reduction in lung cancer mortality with the use of LDCT over chest X-ray (CXR), should such a benefit exist. The trial built upon the PLCO Cancer Screening Trial, which is studying the usefulness of CXR screening compared with community care. Published findings from the Mayo Clinic CT cohort study provide a cautionary note about screening with spiral CT. The researchers compared findings from the historic Mayo Lung Project (intense CXR screening) with findings from a subset of their CT participants who were comparable to the former study's participants in terms of lung cancer risk factors and showed [unreadable]no difference in [unreadable] lung cancer mortality rates[unreadable]. NLST is a well-powered, randomized controlled clinical trial able to assess lung cancer mortality with ample statistical power. NLST began in September 2002 and randomized over 53,000 heavy and/or long-term smokers to low-dose, helical computed tomography (CT) or chest X-ray (CXR). Participants received an initial and two subsequent screening exams. Participants who receive a positive or suspicious screening result are notified and referred to their primary care practitioner to determine appropriate follow up procedures. Screening occurs on sophisticated state-of-the-art equipment in radiology departments with highly qualified staff specifically trained and certified in NLST procedures. The helical CT equipment reflects that currently in use in academic practices across the United States. GE, Siemens, Philips and Toshiba are the CT manufacturers represented. They represent all the manufacturers of this specialty equipment in the world. Importantly, a minimum four-panel detector is required and equipment upgrades to 8, 16 and 64 panel detectors occur as the institutions make capital investments. An intensive quality assurance program has been developed to ensure adherence to harmonized, image acquisition parameters, image quality and dose-minimization parameters. The concept of low-dose helical CT is to optimize image acquisition with the lowest dose possible and take advantage of the contrast provided by lung aeration. Radiation dose is carefully monitored and controlled for all equipment at all sites. Recent evidence announced by the National Academy of Sciences indicates the prudence of minimizing radiation exposure, as doses in the 10 [unreadable] 100 mSv range have been associated with an elevated risk of cancer death in atomic bomb survivors. The low dose screen administered is consonant with a low radiation risk in the 55 [unreadable] 74 year old smokers in the NLST. Participants will be contacted annually to determine current health status. Follow up includes ascertainment of adverse medical outcomes, cancer incidence, cause of death, and mortality impact.